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1.
Artículo en Inglés | MEDLINE | ID: mdl-39485532

RESUMEN

Activating autophagy may be therapeutically beneficial, and we have previously shown that azathioprine (AZA), an immunomodulatory drug, induces autophagy. Here, we evaluated the induction of autophagy by the thiopurines AZA, mercaptopurine (6-MP) and thioguanine (6-TG) in THP-1 macrophages and investigated the mechanism of action in the context of this cellular process. The cytotoxicity of thiopurines was evaluated using an LDH assay. Induction of endogenous LC3 by thiopurines was evaluated using immunostaining. To confirm autophagy activation by thiopurines, a GFP-RFP-LC3 reporter plasmid was used to monitor the maturation of autophagosomes to autolysosomes. Induction of apoptosis by thiopurines was evaluated using Annexin V/PI staining, and ER stress was assessed via RT‒PCR analysis of XBP1 splicing. To gain insight into the mechanism of action of thiopurines, mTORC1 activity and eIF2α-S51 phosphorylation were evaluated by immunoblotting. Thiopurines were not cytotoxic to cells and induced strong time- and concentration-dependent autophagy. Thiopurines activate autophagy with complete progression through the pathway. Induction of autophagy by thiopurines occurred independently of apoptosis and ER stress. Immunoblotting revealed that AZA inhibited mTORC1 activity, and AZA and 6-TG increased eIF2α-S51 phosphorylation. In contrast, 6-MP had a minor effect on either signalling pathway. Thiopurines are strong inducers of autophagy, and autophagy induction should be considered among the mechanisms responsible for patient response to thiopurines.

2.
Artículo en Inglés | MEDLINE | ID: mdl-37569013

RESUMEN

Family support is offered to Australian parents of young children using a mix of targeted and universal child and family health services including nurse-home-visiting programmes. These rely on the voluntary engagement of families. In this study, the capacity to engage and retain families, including those at risk of becoming involved with child protection services, was examined. The broad objective was to identify nursing practices used at the interface of health and child protection services and to articulate those practices. Child and Family Health Nurses (CFHN) (n = 129) participated in a pragmatic, multilevel mixed-methods study. A questionnaire was used to identify nursing practices in the first phase of this study followed by focus groups in the second phase to describe these practices in more detail. Three practice themes were identified and described: enrolment, retention and conclusion of the nurse-family relationship. Universal child and family health services feature flexible, advanced, and multidimensional family support services including child protection practices. This paper focuses on practices employed by nurses to engage and retain families where child protection concerns are identified.

3.
Front Oncol ; 10: 628, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32391281

RESUMEN

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to tumors, it is proving more difficult to personalize radiotherapy regimens based on cancer biology. Biomarkers that provide prognostic or predictive information regarding a tumor's intrinsic radiosensitivity or its response to treatment could prove valuable in helping to personalize radiation dosing, enabling clinicians to make decisions between different treatment options whilst avoiding radiation-induced toxicity in patients unlikely to gain therapeutic benefit. Studies have investigated numerous ways in which both patient and tumor radiosensitivities can be assessed. Tumor molecular profiling has been used to develop radiosensitivity gene signatures, while the assessment of specific intracellular or secreted proteins, including circulating tumor cells, exosomes and DNA, has been performed to identify prognostic or predictive biomarkers of radiation response. Finally, the investigation of biomarkers related to radiation-induced toxicity could provide another means by which radiotherapy could become personalized. In this review, we discuss studies that have used these methods to identify or develop prognostic/predictive signatures of radiosensitivity, and how such assays could be used in the future as a means of providing personalized radiotherapy.

4.
Sci Rep ; 9(1): 19076, 2019 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-31836808

RESUMEN

Neuroendocrine prostate cancer (NEPC) is thought to arise as prostate adenocarcinoma cells transdifferentiate into neuroendocrine (NE) cells to escape potent anti-androgen therapies however, the exact molecular events accompanying NE transdifferentiation and their plasticity remain poorly defined. Cell fate regulator ASCL1/hASH1's expression was markedly induced in androgen deprived (AD) LNCaP cells and prominent nuclear localisation accompanied acquisition of the NE-like morphology and expression of NE markers (NSE). By contrast, androgen-insensitive PC3 and DU145 cells displayed clear nuclear hASH1 localisation under control conditions that was unchanged by AD, suggesting AR signalling negatively regulated hASH1 expression and localisation. Synthetic androgen (R1881) prevented NE transdifferentiation of AD LNCaP cells and markedly suppressed expression of key regulators of lineage commitment and neurogenesis (REST and ASCL1/hASH1). Post-AD, NE LNCaP cells rapidly lost NE-like morphology following R1881 treatment, yet ASCL1/hASH1 expression was resistant to R1881 treatment and hASH1 nuclear localisation remained evident in apparently dedifferentiated LNCaP cells. Consequently, NE cells may not fully revert to an epithelial state and retain key NE-like features, suggesting a "hybrid" phenotype. This could fuel greater NE transdifferentiation, therapeutic resistance and NEPC evolution upon subsequent androgen deprivation. Such knowledge could facilitate CRPC tumour stratification and identify targets for more effective NEPC management.


Asunto(s)
Andrógenos/farmacología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Núcleo Celular/metabolismo , Transdiferenciación Celular , Células Neuroendocrinas/patología , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Transdiferenciación Celular/efectos de los fármacos , Humanos , Masculino , Células Neuroendocrinas/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Transporte de Proteínas/efectos de los fármacos
5.
Sci Rep ; 8(1): 7506, 2018 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-29760395

RESUMEN

Neutrophil surveillance is central to nanoparticle clearance. Silver nanoparticles (AgNP) have numerous uses, however conflicting evidence exists as to their impact on neutrophils and whether they trigger damaging inflammation. Neutrophil's importance in innate defence and regulating immune networks mean it's essential we understand AgNP's impact on neutrophil function. Human neutrophil viability following AgNP or Ag Bulk treatment was analysed by flow cytometry and AnV/PI staining. Whilst AgNP exposure did not increase the total number of apoptotic neutrophils, the number of late apoptotic neutrophils was increased, suggesting AgNP increase transit through apoptosis. Mature (CD16bright/CD62Lbright), immature (CD16dim/CD62Lbright) and apoptotic (CD16dim/CD62Ldim) neutrophil populations were evident within isolated neutrophil preparations. AgNP exposure significantly reduced CD62L staining of CD16bright/CD62Lbright neutrophils, and increased CD16 staining of CD16dim/CD62Lbright populations, suggesting AgNPs trigger neutrophil activation and maturation, respectively. AgNP exposure dramatically increased IL-8, yet not classical pro-inflammatory cytokine release, suggesting AgNP triggers neutrophil activation, without pro-inflammation or damaging, necrotic cell death. For the first time, we show AgNPs differentially affect distinct sub-populations of circulating human neutrophils; activating mature neutrophils with the emergence of CD16bright/CD62Ldim neutrophils. This may stimulate particle clearance without harmful inflammation, challenging previous assumptions that silver nanomaterials induce neutrophil toxicity and damaging inflammatory responses.


Asunto(s)
Interleucina-8/metabolismo , Neutrófilos/citología , Plata/efectos adversos , Regulación hacia Arriba , Supervivencia Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Selectina L/metabolismo , Nanopartículas del Metal/efectos adversos , Activación Neutrófila , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Receptores de IgG/metabolismo
6.
BMC Palliat Care ; 17(1): 63, 2018 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-29669559

RESUMEN

BACKGROUND: Self-care practice within the palliative care workforce is often discussed, yet seemingly under-researched. While palliative care professionals are required to implement and maintain effective self-care strategies, there appears little evidence to guide them. Moreover, there is an apparent need to clarify the meaning of self-care in palliative care practice. This paper reports qualitative findings within the context of a broader mixed-methods study. The aim of the present study was to explore the meaning and practice of self-care as described by palliative care nurses and doctors. METHODS: A purposive sample of 24 palliative care nurses and doctors across Australia participated in semi-structured, in-depth interviews. Interviews were digitally recorded and transcribed prior to inductive qualitative content analysis, supported by QSR NVivo data management software. RESULTS: Three overarching themes emerged from the analysis: (1) A proactive and holistic approach to promoting personal health and wellbeing to support professional care of others; (2) Personalised self-care strategies within professional and non-professional contexts; and (3) Barriers and enablers to self-care practice. CONCLUSIONS: The findings of this study provide a detailed account of the context and complexity of effective self-care practice previously lacking in the literature. Self-care is a proactive, holistic, and personalised approach to the promotion of health and wellbeing through a variety of strategies, in both personal and professional settings, to enhance capacity for compassionate care of patients and their families. This research adds an important qualitative perspective and serves to advance knowledge of both the context and effective practice of self-care in the palliative care workforce.


Asunto(s)
Personal de Salud/psicología , Cuidados Paliativos , Autocuidado/psicología , Adulto , Actitud del Personal de Salud , Australia , Femenino , Salud Holística , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros/psicología , Cuidados Paliativos/psicología , Cuidados Paliativos/normas , Médicos/psicología , Investigación Cualitativa , Autocuidado/métodos , Recursos Humanos
7.
Int J Palliat Nurs ; 24(1): 4-11, 2018 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-29368553

RESUMEN

This study examined levels of, and relationships between, self-care ability, self-compassion, and compassion among palliative care nurses and doctors. METHODS: A total of 369 participants across Australia completed a cross-sectional survey comprising a demographic questionnaire and outcome measures for each variable. Descriptive and inferential statistics were analysed, controlling for potential social-desirability bias. RESULTS: Levels of compassion, self-compassion and self-care ability varied, with some individuals scoring high or low in each. Self-compassion and self-care ability were positively correlated (r = .412, p<.001), whereas a negative correlation was observed between compassion and self-compassion (r = -.122, p<.05). Linear regression further indicated that: increased compassion was associated with a decrease in self-compassion, and increased self-care ability was associated with an increase in self-compassion. CONCLUSION: These results suggest important implications for self-care in the palliative care workforce. Moreover, this study contributes an empirical basis to inform future research and education to promote balanced compassion and compassion literacy in palliative care practice.


Asunto(s)
Empatía , Enfermería de Cuidados Paliativos al Final de la Vida , Enfermeras y Enfermeros , Medicina Paliativa , Médicos , Automanejo , Adolescente , Adulto , Australia , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
8.
PLoS One ; 12(10): e0185664, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28968430

RESUMEN

Stroke causes severe neuronal damage as disrupted cerebral blood flow starves neurons of oxygen and glucose. The hypoxia inducible factors (HIF-1α and HIF-2α) orchestrate oxygen homeostasis and regulate specific aspects of hypoxic adaptation. Here we show the importance of HIF-2α dependant signalling in neuronal adaptation to hypoxic insult. PC12 and NT2 cells were differentiated into neuronal-like cells using NGF and retinoic acid, and exposed to acute hypoxia (1% O2). Gene and protein expression was analysed by qPCR and immunoblotting and the neuronal-like phenotype was examined. PC12 and NT2 differentiation promoted neurite extension and expression of neuronal markers, NSE and KCC2. Induction of HIF-1α mRNA or protein was not detected in hypoxic neuronal-like cells, however marked induction of HIF-2α mRNA and protein expression was observed. Induction of HIF-1α target genes was also not detected in response to acute hypoxia, however significant induction of HIF-2α transcriptional targets was clearly evident. Furthermore, hypoxic insult dramatically reduced both neurite number and length, and attenuated expression of neuronal markers, NSE and KCC2. This correlated with an increase in expression of the neural progenitor and stem cell-like markers, CD44 and vimentin, suggesting HIF-2α molecular mechanisms could potentially promote regression of neuronal-like cells to a stem-like state and trigger neuronal recovery following ischaemic insult. Our findings suggest the HIF-2α pathway predominates over HIF-1α signalling in neuronal-like cells following acute hypoxia.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Hipoxia de la Célula , Neuronas/metabolismo , Transducción de Señal , Adaptación Fisiológica , Animales , Diferenciación Celular , Estrés del Retículo Endoplásmico , Humanos , Células-Madre Neurales/metabolismo , Neuronas/citología , Estabilidad Proteica , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa
9.
Acta Paediatr ; 106(10): 1608-1616, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28685899

RESUMEN

AIM: This study presents results from an intervention designed to improve identification and response to abusive head trauma in a tertiary paediatric hospital in Vietnam. METHODS: One hundred and sixteen healthcare professionals (paediatric medical and nursing staff) completed a clinical training programme and participated in its evaluation. A pre-post-test and follow-up design was used to evaluate the outcomes. Questionnaires were used to collect data prior to training, at six weeks and at six months. Generalised linear modelling was used to examine changes in diagnostic skills and knowledge of the consequences of shaken baby syndrome (SBS) (a form of abusive head trauma), its prevention and treatment. RESULTS: At baseline, awareness and knowledge reflected no former abusive head trauma training. Following the intervention, participants had an increased awareness of shaken baby syndrome and the potential consequences of shaking infants and had acquired techniques to inform parents how to manage the crying infant. CONCLUSION: The intervention was effective in raising awareness of shaken baby syndrome and its consequences amongst the participating healthcare professionals in Vietnam. Training can improve detection and prevention of abusive head trauma, and the intervention has the potential to be adapted for similar settings internationally.


Asunto(s)
Síndrome del Bebé Sacudido/diagnóstico , Competencia Clínica , Humanos , Estudios Longitudinales , Prevención Secundaria , Síndrome del Bebé Sacudido/prevención & control , Vietnam
10.
Int J Palliat Nurs ; 23(5): 219-229, 2017 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-28548918

RESUMEN

INTRODUCTION: Compassion is arguably central to palliative care. However, calls for the restoring of compassionate care suggest a need for greater understanding and promotion of compassion in practice. Drawing upon the Foucauldian concept 'Care of the Self', this review explored the literature relating to palliative care professionals' self-care, self-compassion, and compassion for others. METHODS: Three electronic databases were searched using identified key words. A thematic approach was used to synthesise and critically discuss the literature in the form of a narrative review. RESULTS: Four themes were identified: (1) importance of self-care; (2) awareness, expression, and planning; (3) dimensions of self-care; and (4) balanced compassion. Approaches to self-care practice and research focused mainly on compassion fatigue or a coping paradigm. CONCLUSIONS: This review highlights both the importance and multifaceted nature of palliative care professionals' self-care, in relation to self-compassion and compassion for others. Despite widespread discussion, empirical knowledge of these variables is limited. Future research could usefully explore health promotion interventions in self-care practice, or a positive psychology paradigm that encompasses compassion and self-compassion as positive emotions associated with wellbeing.


Asunto(s)
Adaptación Psicológica , Empatía , Personal de Salud , Cuidados Paliativos , Autocuidado , Desgaste por Empatía , Humanos
11.
J Palliat Med ; 20(6): 625-630, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28092492

RESUMEN

BACKGROUND: Self-care is an important consideration for palliative care professionals. To date, few details have been recorded about the nature or uptake of self-care practices in the palliative care workforce. As part of a broader mixed methods study, this article reports findings from a national survey of nurses and doctors. OBJECTIVE: The objective of this study was to examine perceptions, education, and practices relating to self-care among palliative care nursing and medical professionals. DESIGN: A cross-sectional survey using REDCap software was conducted between April and May 2015. Perceived importance of self-care, self-care education and planning, and self-care strategies most utilized were explored. Descriptive statistics were calculated and content analysis used to identify domains of self-care. SETTING/SUBJECTS: Three hundred seventy-two palliative care nursing and medical professionals practicing in Australia. RESULTS: Most respondents regarded self-care as very important (86%). Some rarely practised self-care and less than half (39%) had received training in self-care. Physical self-care strategies were most commonly reported, followed closely by social self-care and inner self-care. Self-care plans had been used by a small proportion of respondents (6%) and over two-thirds (70%) would consider using self-care plans if training could be provided. CONCLUSIONS: Self-care is practised across multiple health related domains, with physical self-care strategies used most frequently. Australian palliative care nurses and doctors recognize the importance of self-care practice, but further education and training are needed to increase their understanding of, and consistency in, using effective self-care strategies. These findings carry implications for professional practice and future research.


Asunto(s)
Personal de Salud/psicología , Enfermería de Cuidados Paliativos al Final de la Vida , Cuidados Paliativos , Autocuidado , Adolescente , Adulto , Australia , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
12.
Int J Nurs Stud ; 64: 72-85, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27693983

RESUMEN

BACKGROUND: The development of child behaviour and parenting difficulties is understood to undermine treatment outcomes for children with atopic dermatitis. Past research has reported on correlates of child behaviour difficulties. However, few research studies have sought to examine parenting confidence and practices in this clinical group. OBJECTIVES: To examine relationships between child, parent, and family variables, parent-reported and directly-observed child and parent behaviour, parents' self-efficacy with managing difficult child behaviour, self-reported parenting strategies, and disease severity. DESIGN: Cross-sectional study design. PARTICIPANTS: Parent-child dyads (N=64) were recruited from the dermatology clinic of a paediatric tertiary referral hospital in Brisbane, Australia. Children had a diagnosis of atopic dermatitis of ≥3months and no other chronic health conditions except asthma, allergic rhinitis, or allergy. METHODS: Parents completed self-report measures assessing child behaviour; parent depression, anxiety, and stress; parenting conflict and relationship satisfaction; self-efficacy with managing difficult child behaviour, and use of ineffective parenting strategies; and self-efficacy for managing atopic dermatitis, and performance of atopic dermatitis management tasks. The Scoring Atopic Dermatitis index was used to assess disease severity. Routine at-home treatment sessions were coded for parent and child behaviour. RESULTS: Pearson's and Spearman's correlations identified relationships (p<0.05) between self-efficacy with managing difficult child behaviour and child behaviour problems, parent depression and stress, parenting conflict and relationship satisfaction, and household income. There were also relationships between each of these variables and use of ineffective parenting strategies. Greater use of ineffective parenting strategies was associated with more severe atopic dermatitis. Using multiple linear regressions, child behaviour and household income explained unique variance in self-efficacy for managing difficult child behaviour; household income alone explained unique variance in use of ineffective parenting strategies. Self-efficacy for managing difficult child behaviour and self-efficacy for managing atopic dermatitis were positively correlated (rho=0.48, p<0.001), and more successful self-reported performance of atopic dermatitis management tasks correlated with less permissive (r=0.35, p=0.005) and less authoritarian (r=0.41, p=0.001) parenting. Directly observed aversive child behaviour was associated with more severe atopic dermatitis, parent stress, and parent-reported child behaviour problems. CONCLUSION: This study revealed relationships between parents' self-efficacy and parenting practices across the domains of child behaviour management and atopic dermatitis management. Parents of children with more severe atopic dermatitis may have difficulty responding to child behaviour difficulties appropriately, potentially impacting on illness management. Incorporating parent and parenting support within treatment plans may improve not only child and family wellbeing, but also treatment outcomes.


Asunto(s)
Conducta Infantil , Dermatitis Atópica/terapia , Responsabilidad Parental/psicología , Índice de Severidad de la Enfermedad , Cuidados de la Piel/métodos , Adulto , Australia , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Renta , Masculino , Autoeficacia , Encuestas y Cuestionarios , Resultado del Tratamiento
13.
Int J Nurs Stud ; 52(1): 216-28, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25441758

RESUMEN

BACKGROUND: Successful management of atopic dermatitis poses a significant and ongoing challenge to parents of affected children. Despite frequent reports of child behaviour problems and parenting difficulties, there is a paucity of literature examining relationships between child behaviour and parents' confidence and competence with treatment. OBJECTIVES: To examine relationships between child, parent, and family variables, parents' self-efficacy for managing atopic dermatitis, self-reported performance of management tasks, observed competence with providing treatment, and atopic dermatitis severity. DESIGN: Cross-sectional study design. Participants A sample of 64 parent-child dyads was recruited from the dermatology clinic of a paediatric tertiary referral hospital in Brisbane, Australia. METHODS: Parents completed self-report questionnaires examining child behaviour, parents' adjustment, parenting conflict, parents' relationship satisfaction, and parents' self-efficacy and self-reported performance of key management tasks. Severity of atopic dermatitis was assessed using the Scoring Atopic Dermatitis index. A routine home treatment session was observed, and parents' competence in carrying out the child's treatment assessed. RESULTS: Pearson's and Spearman's correlations identified significant relationships (p<.05) between parents' self-efficacy and disease severity, child behaviour difficulties, parent depression and stress, parenting conflict, and relationship satisfaction. There were also significant relationships between each of these variables and parents' self-reported performance of management tasks. More profound child behaviour difficulties were associated with more severe atopic dermatitis and greater parent stress. Using multiple linear regressions, significant proportions of variation in parents' self-efficacy and self-reported task performance were explained by child behaviour difficulties and parents' formal education. Self-efficacy emerged as a likely mediator for relationships between both child behaviour and parents' education, and self-reported task performance. Direct observation of treatment sessions revealed strong relationships between parents' treatment competence and parents' self-efficacy, outcome expectations, and self-reported task performance. Less competent task performance was also associated with greater parent-reported child behaviour difficulties, parent depression and stress, parenting conflict, and relationship dissatisfaction. CONCLUSION: This study revealed the importance of child behaviour to parents' confidence and practices in the context of atopic dermatitis management. Children with more severe atopic dermatitis are at risk of presenting with challenging behaviour problems and their parents struggle to manage the condition successfully.


Asunto(s)
Dermatitis Atópica/terapia , Padres/psicología , Adulto , Niño , Conducta Infantil , Estudios Transversales , Dermatitis Atópica/fisiopatología , Dermatitis Atópica/psicología , Emociones , Humanos , Autoeficacia , Índice de Severidad de la Enfermedad
15.
J Mol Biol ; 427(8): 1728-47, 2015 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-25543083

RESUMEN

Mouse double minute 2 (MDM2) has a phosphorylation site within a lid motif at Ser17 whose phosphomimetic mutation to Asp17 stimulates MDM2-mediated polyubiquitination of p53. MDM2 lid deletion, but not Asp17 mutation, induced a blue shift in the λ(max) of intrinsic fluorescence derived from residues in the central domain including Trp235, Trp303, Trp323, and Trp329. This indicates that the Asp17 mutation does not alter the conformation of MDM2 surrounding the tryptophan residues. In addition, Phe235 mutation enhanced MDM2 binding to p53 but did not stimulate its ubiquitination function, thus uncoupling increases in p53 binding from its E3 ubiquitin ligase function. However, the Asp17 mutation in MDM2 stimulated its discharge of the UBCH5a-ubiquitin thioester adduct (UBCH5a is a ubiquitin-conjugating enzyme E2D 1 UBC4/5 homolog yeast). This stimulation of ubiquitin discharge from E2 was independent of the p53 substrate. There are now four known effects of the Asp17 mutation on MDM2: (i) it alters the conformation of the isolated N-terminus as defined by NMR; (ii) it induces increased thermostability of the isolated N-terminal domain; (iii) it stimulates the allosteric interaction of MDM2 with the DNA-binding domain of p53; and (iv) it stimulates a novel protein-protein interaction with the E2-ubiquitin complex in the absence of substrate p53 that, in turn, increases hydrolysis of the E2-ubiquitin thioester bond. These data also suggest a new strategy to disrupt MDM2 function by targeting the E2-ubiquitin discharge reaction.


Asunto(s)
Mutación Puntual , Poliubiquitina/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Regulación Alostérica , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Humanos , Hidrólisis , Ratones , Datos de Secuencia Molecular , Conformación Proteica , Estructura Terciaria de Proteína , Proteínas Proto-Oncogénicas c-mdm2/química , Proteína p53 Supresora de Tumor/química , Ubiquitina/metabolismo , Ubiquitinación
16.
Arthroscopy ; 30(2): 195-201, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24485112

RESUMEN

PURPOSE: To determine whether patients with higher levels of preoperative psychological distress more frequently use a postoperative fascia iliaca nerve block for pain control after hip arthroscopy, and to determine whether a fascia iliaca nerve block is an effective adjunct to multimodal oral and intravenous analgesia after hip arthroscopy. METHODS: One hundred seven patients undergoing hip arthroscopy were prospectively enrolled. Before surgery, patients were administered the Distress Risk Assessment Method questionnaire to quantify their level of preoperative psychological distress. Postoperatively, patients with pain inadequately controlled by multimodal oral and intravenous analgesics could request and receive a fascia iliaca nerve block. Pain scores, opioid consumption, time in the post-anesthesia care unit (PACU), and postoperative complications were recorded for all patients. RESULTS: Patients with normal Distress Risk Assessment Method scores requested fascia iliaca nerve blocks approximately half as frequently (18 of 50 [36%]) as patients in the at-risk category (28 of 47 [60%]) or distressed category (7 of 10 [70%]) (P = .02). Patients with high levels of distress also received 40% more intraoperative opioid than patients with normal scores (P = .04). In the study population as a whole, patients who received a fascia iliaca nerve block (n = 53) had a higher initial visual analog scale (VAS) pain score in the PACU (7.2 ± 0.3 v 5.5 ± 0.4, P = .001) and showed greater improvement in the VAS pain score by PACU discharge (-4.3 ± 0.2 v -2.1 ± 0.3, P ≤ .0001) compared with patients who did not receive a block (n = 54). CONCLUSIONS: Patients with higher levels of preoperative psychological distress more frequently requested a postoperative nerve block to achieve adequate pain control after hip arthroscopy. Patients receiving a block had greater improvement in VAS pain scores compared with patients managed with oral and intravenous analgesics alone. LEVEL OF EVIDENCE: Level IV, case series.


Asunto(s)
Analgésicos/uso terapéutico , Artroscopía , Articulación de la Cadera/cirugía , Manejo del Dolor/métodos , Dolor Postoperatorio/terapia , Estrés Psicológico/complicaciones , Adulto , Analgesia/métodos , Femenino , Humanos , Artropatías/psicología , Artropatías/cirugía , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Bloqueo Nervioso/métodos , Dimensión del Dolor , Dolor Postoperatorio/complicaciones , Dolor Postoperatorio/psicología , Estudios Prospectivos , Estrés Psicológico/psicología
17.
Int J Inj Contr Saf Promot ; 21(3): 227-35, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23768210

RESUMEN

A retrospective, descriptive analysis of a sample of children under 18 years presenting to a hospital emergency department (ED) for treatment of an injury was conducted. The aim was to explore characteristics and identify differences between children assigned abuse codes and children assigned unintentional injury codes using an injury surveillance database. Only 0.1% of children had been assigned the abuse code and 3.9% a code indicating possible abuse. Children between 2 and 5 years formed the largest proportion of those coded to abuse. Superficial injury and bruising were the most common types of injury seen in children in the abuse group and the possible abuse group (26.9% and 18.8%, respectively), whereas those with unintentional injury were most likely to present with open wounds (18.4%). This study demonstrates that routinely collected injury surveillance data can be a useful source of information for describing injury characteristics in children assigned abuse codes compared to those assigned no abuse codes.


Asunto(s)
Maltrato a los Niños/diagnóstico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Adolescente , Factores de Edad , Niño , Maltrato a los Niños/estadística & datos numéricos , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Vigilancia de la Población/métodos , Queensland/epidemiología , Estudios Retrospectivos , Heridas y Lesiones/epidemiología , Heridas y Lesiones/etiología
18.
Can J Anaesth ; 59(4): 394-407, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22407474

RESUMEN

PURPOSE: There are more than 200,000 Canadians living with permanent pacemakers or implantable defibrillators, many of whom will require surgery or invasive procedures each year. They face potential hazards when undergoing surgery; however, with appropriate planning and education of operating room personnel, adverse device-related outcomes should be rare. This joint position statement from the Canadian Cardiovascular Society (CCS) and the Canadian Anesthesiologists' Society (CAS) has been developed as an accessible reference for physicians and surgeons, providing an overview of the key issues for the preoperative, intraoperative, and postoperative care of these patients. PRINCIPAL FINDINGS: The document summarizes the limited published literature in this field, but for most issues, relies heavily on the experience of the cardiologists and anesthesiologists who contributed to this work. This position statement outlines how to obtain information about an individual's type of pacemaker or implantable defibrillator and its programming. It also stresses the importance of determining if a patient is highly pacemaker-dependent and proposes a simple approach for nonelective evaluation of dependency. Although the document provides a comprehensive list of the intraoperative issues facing these patients, there is a focus on electromagnetic interference resulting from electrocautery and practical guidance is given regarding the characteristics of surgery, electrocautery, pacemakers, and defibrillators which are most likely to lead to interference. CONCLUSIONS: The document stresses the importance of preoperative consultation and planning to minimize complications. It reviews the relative merits of intraoperative magnet use vs reprogramming of devices and gives examples of situations where one or the other approach is preferable.


Asunto(s)
Estimulación Cardíaca Artificial , Desfibriladores Implantables , Terapia por Estimulación Eléctrica/instrumentación , Enfermedades del Sistema Nervioso/terapia , Atención Perioperativa , Anestesiología/organización & administración , Cardiología/organización & administración , Humanos , Cuidados Intraoperatorios , Magnetismo , Cuidados Posoperatorios , Sociedades Médicas
19.
Can J Cardiol ; 28(2): 141-51, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22433577

RESUMEN

There are more than 200,000 Canadians living with permanent pacemakers or implantable defibrillators, many of whom will require surgery or invasive procedures each year. They face potential hazards when undergoing surgery; however, with appropriate planning and education of operating room personnel, adverse device-related outcomes should be rare. This joint position statement from the Canadian Cardiovascular Society (CCS) and the Canadian Anesthesiologists' Society (CAS) has been developed as an accessible reference for physicians and surgeons, providing an overview of the key issues for the preoperative, intraoperative, and postoperative care of these patients. The document summarizes the limited published literature in this field, but for most issues, relies heavily on the experience of the cardiologists and anesthesiologists who contributed to this work. This position statement outlines how to obtain information about an individual's type of pacemaker or implantable defibrillator and its programming. It also stresses the importance of determining if a patient is highly pacemaker-dependent and proposes a simple approach for nonelective evaluation of dependency. Although the document provides a comprehensive list of the intraoperative issues facing these patients, there is a focus on electromagnetic interference resulting from electrocautery and practical guidance is given regarding the characteristics of surgery, electrocautery, pacemakers, and defibrillators which are most likely to lead to interference. The document stresses the importance of preoperative consultation and planning to minimize complications. It reviews the relative merits of intraoperative magnet use vs reprogramming of devices and gives examples of situations where one or the other approach is preferable.


Asunto(s)
Arritmias Cardíacas/cirugía , Desfibriladores Implantables , Electrodos Implantados , Enfermedades del Sistema Nervioso/cirugía , Marcapaso Artificial , Atención Perioperativa , Estimulación Cardíaca Artificial , Cardioversión Eléctrica , Humanos
20.
Kaohsiung J Med Sci ; 28(1): 44-53, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22226061

RESUMEN

Taiwan nurses are mandated to report known or suspected child abuse and neglect (CAN), and self-efficacy is known to have an important influence on professional behaviors. The aim of this study was to develop and test the CAN reporting self-efficacy (CANRSE) scale as a measure of nurses' self-efficacy to report CAN. A sample of 496 nurses from Southern Taiwanese hospitals used the CANRSE scale. The psychometric evaluation of the scale included content validity, exploratory and confirmatory factor analyses, convergent validity, as well as Cronbach's α and test-retest reliability. Satisfactory internal consistency (Cronbach's α = 0.92) and test-retest reliability were demonstrated. Confirmatory factor analysis supported the proposed models as having acceptable model fit. Exploratory factor analysis and regression analyses showed that the CANRSE scale had good construct validity and criterion-related validity, respectively. Convergent validity was tested using the general self-efficacy scale and was found to be satisfactory (r = 0.53). The results indicate the CANRSE is reliable and valid, and further testing of its predictive validity is recommended. It can be used to examine the influence of professional self-efficacy in recognizing and reporting CAN cases and to evaluate the impact of training programs aimed at improving CAN reporting.


Asunto(s)
Enfermeras y Enfermeros , Autoeficacia , Encuestas y Cuestionarios , Adulto , Niño , Maltrato a los Niños , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto Joven
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